chr11-32428115-G-A

Variant names:

• chr11-32428115-G-A
• rs2234585
• NM_024426.6:c.785-57C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024426.6(WT1):​c.785-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,478,162 control chromosomes in the GnomAD database, including 35,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4535 hom., cov: 33)
  • Exomes 𝑓: 0.18 (31199 hom.)
• Consequence: WT1 NM_024426.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.500
• Publications: 8 publications found

Genes affected

WT1 (HGNC:12796): (WT1 transcription factor) This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015]

WT1 Gene-Disease associations (from GenCC):

• Denys-Drash syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
• Wilms tumor 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Frasier syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-32428115-G-A is Benign according to our data. Variant chr11-32428115-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024426.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WT1	NM_024426.6	MANE Select	c.785-57C>T		intron	N/A	NP_077744.4
	WT1	NM_024424.5		c.785-57C>T		intron	N/A	NP_077742.3	H0Y7K5
	WT1	NM_001407044.1		c.785-57C>T		intron	N/A	NP_001393973.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WT1	ENST00000452863.10	TSL:1 MANE Select	c.785-57C>T		intron	N/A	ENSP00000415516.5	P19544-7
	WT1	ENST00000639563.4	TSL:1	c.785-57C>T		intron	N/A	ENSP00000492269.3	P19544-8
	WT1	ENST00000332351.9	TSL:1	c.785-57C>T		intron	N/A	ENSP00000331327.5	J3KNN9

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32269 AN: 152062 Hom.: 4505 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.184 AC: 244490 AN: 1325982 Hom.: 31199 AF XY: 0.189 AC XY: 122837 AN XY: 650402

African (AFR) AF: 0.208 AC: 6414 AN: 30840

American (AMR) AF: 0.369 AC: 11806 AN: 31984

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 3788 AN: 21482

East Asian (EAS) AF: 0.693 AC: 26028 AN: 37582

South Asian (SAS) AF: 0.388 AC: 28281 AN: 72952

European-Finnish (FIN) AF: 0.180 AC: 8583 AN: 47568

Middle Eastern (MID) AF: 0.225 AC: 1092 AN: 4846

European-Non Finnish (NFE) AF: 0.143 AC: 146733 AN: 1023706

Other (OTH) AF: 0.214 AC: 11765 AN: 55022

GnomAD4 genome AF: 0.213 AC: 32340 AN: 152180 Hom.: 4535 Cov.: 33 AF XY: 0.223 AC XY: 16576 AN XY: 74390

African (AFR) AF: 0.202 AC: 8386 AN: 41524

American (AMR) AF: 0.316 AC: 4839 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3470

East Asian (EAS) AF: 0.718 AC: 3693 AN: 5146

South Asian (SAS) AF: 0.426 AC: 2051 AN: 4820

European-Finnish (FIN) AF: 0.188 AC: 1990 AN: 10602

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10046 AN: 68002

Other (OTH) AF: 0.228 AC: 482 AN: 2112

Alfa AF: 0.172 Hom.: 302

Bravo AF: 0.222

Asia WGS AF: 0.581 AC: 2020 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.78
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2234585;

hg19: chr11-32449661;